The focus of this research is the study of the chemistry of complexes consisting of polyammonium macrocycles (receptors) and anions (substrates). Preliminary studies have shown that high affinity complexes are formed between the receptor molecules and phosphate derivatives, and these "supramolecular complexes" undergo chemical transformations. Significant rate accelerations are noted in the dephosphorylation of ATP, ADP, pyrophosphate, and formyl phosphate. Two prominent features of the reaction are nucleophilic catalysis and metal ion regulation. The goal of this proposal is to analyze the chemistry of the reactions of polyammonium macrocycles with ATP, ADP, pyrophosphate, and acyl phosphates. The specific receptor molecules to be used in this study are macrocycles ranging in size from 24 to 32 ring atoms and modified rings containing pendant or bridging groups. The specific aims described in the proposal address the following: 1. affinity and specificity in complex formation, 2. structure of active (productive) and inactive (non-productive) complexes, 3. electrostatic catalysis, 4. general-acid general-base catalysis, 5. covalent (nucleophilic) catalysis, and 6. metal ion catalysis. General methodology proposed for this study includes the determination of pKas, stability constants, and stoichiometry. Kinetic studies will include the determination of activation parameters, isotope incorporation, and chiral phosphate analysis. Structural studies will employ multinuclear NMR and X-ray crystallographic analysis. The results of this research should be instrumental to the design of artificial catalysts. In addition, these studies should provide fundamental information on the chemistry of these high-energy substrates and the mechanisms of their reactions with enzymes.